Autoimmunity in New Zealand mice has a genetic and immune basis; however, expression of severity can be modified by viral and other environmental factors as well as sex hormones. The immunologic factors are complex. These include excessive B-cell activation and abnormal T cell function. Excessive B-cell activation can be modified by introducing the X chromosome of a CBA/N mouse into the NZB autoimmune background. The CBA/N X chromosome, which codes for defects in B-cell maturation (xid), causes a reduction in autoimmunity in F1 mice, and in congenic mice. The B cell subset absent in CBA/N mice is that which is hyperactive in NZB mice. In contrast, MRL/1 mice produce autoantibodies via a different B cell subset. Administration of polyclonal B-cell activators (poly rI rC and LPS) bypasses the xid in NZB hybrids and congenic mice in that other subsets of B cells are stimulated to produce autoantibodies. BXSB mice have a Y chromosome-linked gene which accelerates autoimmunity in autoimmune mice, but does not cause it in non-autoimmune mice.